Aminoethoxybenzyl alcohols are widely useful as intermediates for the preparation of various pharmaceuticals. For example, conversion of the benzylic alcohol to a halogen results in the appropriate intermediate for the preparation of indole based estrogen receptor modulators as described in, for example, U.S. Pat. No. 5,998,402. Additionally, similar benzylic halides that can be derived from their corresponding benzylic alcohols have been described as intermediates used in the preparation of compounds known to have inhibitory activity against various matrix metalloproteinase enzymes as well as against tumor necrosis factor α converting enzyme (TACE) (see, e.g., U.S. Pat. No. 5,929,097).
Previous processes for preparing aminoethoxybenzyl alcohols are reported in U.S. Pat. Nos. 6,005,102, 6,242,605 and 6,268,504, as well as PCT Pat. Appln. No. WO 99/19293. Reports of preparation of related compounds can also be found in German patent document, DE 4438028. A summary of such a method is shown in Scheme I:

The reported synthetic methods employ unstable materials such as haloethylamines, which are well known to be difficult to handle (see, e.g., Ludwig Knorr, Berichte, (1904) 37: 3507). The multi-step procedures also reportedly employ dimethylformamide (DMF) as solvent, an expensive and difficult solvent to handle, especially in large scale preparations. Accordingly, more efficient methods for preparing aminoethoxybenzyl alcohols are needed. The processes and intermediates described herein help meet these and other needs.